Patients with head-injury tend to develop secondary complications that may include brain swelling, impaired cerebral circulation, and cerebral ischemia. The goal of this work is to model the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow. This model will provide the basis for a method to continuously assess cerebrovascular autoregulation of patients with brain injury, thereby permitting improved intensive care management and therapy. When autoregulation is intact, the cerebrovascular bed constricts and dilates in response to increases and decreases of cerebral perfusion pressure (CPP). When autoregulation is impaired, changes in the caliber of vessels within the cerebrovascular bed passively follow changes of CPP. Recently, we have applied system identification modeling techniques to laboratory and clinical recordings of ICP and arterial blood pressure (ABP) to examine changes in the highest modal frequency (HMF) of cerebrovascular pressure transmission. From findings based on an analysis of these pressure recordings, the following hypothesis has been developed: When autoregulation is intact, changes of the HMF are inversely related to changes of cerebral perfusion pressure (CPP) and resistance of the arterial-arteriolar bed. In contrast, when cerebrovascular tension is passive, changes of HMF are directly related to changes of CPP and resistance of the arterial-arteriolar bed. To test this hypothesis, the following three specific aims will be addressed using piglets. Using the piglet equipped with a cranial window, we will determine the relationships between changes of arteriolar diameter, cerebral blood flow measured by laser Doppler and by hydrogen clearance method, CPP, and the HMF during intact and impaired pressure regulation induced by manipulation of arterial blood gases. Furthermore, we will determine these same relationships for changes induced by inappropriate vasodilation during artificially elevated ABP. Simulation of ICP with a third order windkessel model of intracranial pressure dynamics will be used to examine the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow. [unreadable] [unreadable]